Mitochondrial diseases encompass at least 40 diverse disorders that are grouped because of their links to mitochondrial failure. These diseases can occur following inheritance or spontaneous mutations in mitochondrial or nuclear DNA that lead to altered functions of the mitochondrial proteins (or RNA). Depending on the target cell and/or tissues affected, symptoms resulting from mitochondrial diseases may include altered motor control; altered muscle output; gastrointestinal dysfunction; altered growth; diabetes; seizures; visual/hearing problems; lactic acidosis; developmental delays; and susceptibility to infection or cardiac, liver, and respiratory disease. Although there is evidence for tissue-specific isoforms of mitochondrial proteins, mutations in these proteins do not fully explain the highly variable patterns or targeted organ systems observed with mitochondrial diseases.

THERAPEUTIC HIGHLIGHTS

With the diversity of disease types and the overall importance of mitochondria in energy production, it is not surprising that there is no single cure for mitochondrial diseases and focus remains on treating the symptoms when possible. For example, in some mitochondrial myopathies (ie, mitochondrial diseases associated with neuromuscular function), physical therapy may help extend the range of movement of muscles and improve dexterity.

The enzyme complexes responsible for oxidative phosphorylation illustrate the interactions between the products of the mitochondrial genome and the nuclear genome. For example, complex I, reduced nicotinamide adenine dinucleotide dehydrogenase (NADH), is made up of 7 protein subunits coded by mitochondrial DNA and 39 subunits coded by nuclear DNA. Complex II, succinate dehydrogenase-ubiquinone oxidoreductase; complex III, ubiquinonecytochrome c oxidoreductase; and complex IV, cytochrome c oxidase, act with complex I, coenzyme Q, and cytochrome c to convert metabolites to CO2 and water. Complexes I, III, and IV pump protons (H+) into the intermembrane space during this electron transfer. The protons then flow down their electrochemical gradient through complex V, ATP synthase, which harnesses this energy to generate ATP.